Control of signaling-mediated clearance of apoptotic cells by the tumor suppressor p53

The inefficient clearance of dying cells can lead to abnormal immune responses, such as unresolved inflammation and autoimmune conditions. We show that tumor suppressor p53 controls signaling-mediated phagocytosis of apoptotic cells through its target, Death Domain1α (DD1α), which suggests that p53 promotes both the proapoptotic pathway and postapoptotic events. DD1α appears to function as an engulfment ligand or receptor that engages in homophilic intermolecular interaction at intercellular junctions of apoptotic cells and macrophages, unlike other typical scavenger receptors that recognize phosphatidylserine on the surface of dead cells. DD1α-deficient mice showed in vivo defects in clearing dying cells, which led to multiple organ damage indicative of immune dysfunction. p53-induced expression of DD1α thus prevents persistence of cell corpses and ensures efficient generation of precise immune responses

Patient Experience Factors and Implications for Improvement Based on the Treatment Journey of Patients with Head and Neck Cancer

Based on the treatment journey, this study aimed to present insights into improving the patient-centered service experience for head and neck cancer (HNC) patients. We interviewed and observed patients, caregivers, and doctors. We conducted a qualitative content analysis and service clue analysis to identify barriers and enablers to patient care and to derive insights into the patient experience (PE). We received feedback from doctors considering the priority, importance, and feasibility of improvements and classified the insights into three service experience aspects, to suggest improvement directions. As a result, the ‘functional’ aspect of service experience stressed the importance of a comprehensive guide to the treatment process, delivery of reliable information, use of easy-to-understand terms, repeated summary explanations, the establishment of close and flexible linkages between departments, and the provision of educational programs. Regarding the ‘mechanic’ aspect, the use of large and clear visuals for patients, to easily understand the care information provided by medical staff was distinguished. In the ‘humanic’ aspect, patients’ psychological stability, trust in doctors, and doctor’s encouragement and support through maintaining a positive attitude were prioritized. This qualitative study provided integrative insights into the HNC patient experience, through the application of service design methodologies, such as a patient journey map, participatory research methods, and service experience clues

Evaluation of In Vivo Prepared Albumin-Drug Conjugate Using Immunoprecipitation Linked LC-MS Assay and Its Application to Mouse Pharmacokinetic Study

There have been many attempts in pharmaceutical industries and academia to improve the pharmacokinetic characteristics of anti-tumor small-molecule drugs by conjugating them with large molecules, such as monoclonal antibodies, called ADCs. In this context, albumin, one of the most abundant proteins in the blood, has also been proposed as a large molecule to be conjugated with anti-cancer small-molecule drugs. The half-life of albumin is 3 weeks in humans, and its distribution to tumors is higher than in normal tissues. However, few studies have been conducted for the in vivo prepared albumin-drug conjugates, possibly due to the lack of robust bioanalytical methods, which are critical for evaluating the ADME/PK properties of in vivo prepared albumin-drug conjugates. In this study, we developed a bioanalytical method of the albumin-conjugated MAC glucuronide phenol linked SN-38 ((2S,3S,4S,5R,6S)-6-(4-(((((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano [3′,4′:6,7] indolizino [1,2-b] quinolin-9-yl)oxy)methyl)(2 (methylsulfonyl)ethyl)carbamoyl)oxy)methyl)-2-(2-(3-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-N-methylpropanamido)acetamido)phenoxy)-3,4,5-trihydroxytetra-hydro-2H-pyran-2-carboxylic acid) as a proof-of-concept. This method is based on immunoprecipitation using magnetic beads and the quantification of albumin-conjugated drug concentration using LC-qTOF/MS in mouse plasma. Finally, the developed method was applied to the in vivo intravenous (IV) mouse pharmacokinetic study of MAC glucuronide phenol-linked SN-38

Li₁₃Mn(SeO₃)₈: Lithium-Rich Transition Metal Selenite Containing Jahn–Teller Distortive Cations

A novel lithium-rich transition metal selenite, Li₁₃Mn­(SeO₃)₈, that is composed of a Jahn–Teller distortive cation, Mn³⁺, in the high spin d⁴ state, and a second-order Jahn–Teller (SOJT) distortive lone pair cation, Se⁴⁺, has been synthesized via hydrothermal and high temperature solid state reactions. The selenite is classified as a molecular compound consisting of MnO₆ octahedra, SeO₃ trigonal pyramids, and Li⁺ cations. Considering the Li–O interactions, the structure of Li₁₃Mn­(SeO₃)₈ may be described as a pseudo-three-dimensional framework as well. The title compound is thermally stable up to 500 °C and starts decomposing above the temperature attributable to the volatilization of SeO₂. While the MnO₆ octahedra in Li₁₃Mn­(SeO₃)₈ exhibit six identical Mn–O bond distances at room temperature due to the dynamic Jahn–Teller effect, a clear elongation of two Mn–O bonds along a specific direction is observed at 100 K. A series of isostructural selenites with different transition metals, i.e., Li₁₃M­(SeO₃)₈ (M = Sc, Cr, and Fe), have been also successfully obtained in phase pure forms using similar synthetic methods. Magnetic properties, spectroscopic characterizations, and local dipole moments calculations for all the synthesized selenites are presented

The High Performance of Crystal Water Containing Manganese Birnessite Cathodes for Magnesium Batteries

Rechargeable magnesium batteries have lately received great attention for large-scale energy storage systems due to their high volumetric capacities, low materials cost, and safe characteristic. However, the bivalency of Mg²⁺ ions has made it challenging to find cathode materials operating at high voltages with decent (de)­intercalation kinetics. In an effort to overcome this challenge, we adopt an unconventional approach of engaging crystal water in the layered structure of <i>Birnessite</i> MnO₂ because the crystal water can effectively screen electrostatic interactions between Mg²⁺ ions and the host anions. The crucial role of the crystal water was revealed by directly visualizing its presence and dynamic rearrangement using scanning transmission electron microscopy (STEM). Moreover, the importance of lowering desolvation energy penalty at the cathode–electrolyte interface was elucidated by working with water containing nonaqueous electrolytes. In aqueous electrolytes, the decreased interfacial energy penalty by hydration of Mg²⁺ allows <i>Birnessite</i> MnO₂ to achieve a large reversible capacity (231.1 mAh g^–1) at high operating voltage (2.8 V vs Mg/Mg²⁺) with excellent cycle life (62.5% retention after 10000 cycles), unveiling the importance of effective charge shielding in the host and facile Mg²⁺ ions transfer through the cathode’s interface